Search Results (2,470)

Recently, the increasing concern for climate control has led to the widespread application of grid-connected inverter (GIC)-based renewable-energy systems. In addition, the increased usage of non-linear loads and electrification of the transport sector cause ineffective grid-frequency management and the introduction of harmonics. These grid conditions affect power quality and result in uncertainty and inaccuracy in monitoring and measurement. Incorrect measurement leads to overbilling/underbilling, ineffective demand and supply forecasts for the power system, and inefficient performance analysis. To address the outlined problem, a novel, three-phase frequency component extraction and power measurement method based on Digital Lock-in Amplifier (DLIA) and Digital Lock-in Amplifier–Frequency-Locked Loop (DLIA–FLL) is proposed to provide accurate measurements under the conditions of harmonics and frequency offset. A combined filter, with a lowpass filter and notch filter, is employed to improve computation speed for DLIA. A comparative study is performed to verify the effectiveness of the proposed power measurement approach, by comparing the proposed method to the windowed interpolated fast Fourier transform (WIFFT). The ZERA COM 3003 (a commercial high-accuracy power measurement instrument) is used as the reference instrument in the experiment Full article

Advanced high-strength steels (AHSSs) with Zn coatings are commonly joined by the resistance spot welding (RSW) technique. However, Zn coatings could possibly cause the formation of liquid metal embrittlement (LME) cracks during the RSW process. The role of a Zn coating in the tensile–shear fatigue properties of a welding joint has not been systematically explored. In this study, the fatigue properties of tensile–shear RSW joints for bare and Zn-coated advanced high-strength steel (AHSS) specimens were comparatively studied. In particular, more severe LME cracks were triggered by employing a tilted welding electrode because much more stress was caused in the joint. LME cracks had clearly occurred in the Zn-coated steel RSW joints, as observed via optical microscopy. On the contrary, no LME cracks could be found in the RSW joints prepared with the bare steel sheets. The fatigue test results showed that the tensile–shear fatigue properties remained nearly unchanged, regardless of whether bare or Zn-coated steel was used for the RSW joints. Furthermore, Zn mapping adjacent to the crack initiation source was obtained by an electron probe micro-analyzer (EPMA), and it showed no segregation of the Zn element. Thus, the failure of the RSW joints with the Zn coating had not initiated from the LME cracks. It was concluded that the fatigue cracks were initiated by the stress concentration in the notch position between the two bonded steel sheets. Full article

Reinforcing crack-damaged concrete structures with ultra-high-performance concrete (UHPC) proves to be more time-, labor-, and cost-efficient than demolishing and rebuilding under the dual-carbon strategy. In this study, the extended finite element method (XFEM) in ABAQUS was first employed to develop a numerical model of UHPC-reinforced single-notched concrete (U+SNC) beams, analyze their crack extension behavior, and obtain the parameters necessary for calculating fracture toughness. Subsequently, the fracture toughness and instability toughness of U+SNC were calculated using the improved double K fracture criterion. The effects of varying crack height ratios (a/h) of SNC, layer thicknesses (d) of UHPC reinforcement, and fiber contents in UHPC (V_SF) on the fracture properties of U+SNC beams were comprehensively investigated. The results indicate that (1) the UHPC reinforcement layer significantly enhances the load-carrying capacity and crack resistance of the U+SNC beams. Crack extension in the reinforced beams occurs more slowly than in the unreinforced beams; |(2) the fracture performance of the U+BNC beams increases exponentially with d. Considering both the reinforcement effect benefit and beam deadweight, the optimal cost-effective performance is achieved when d is 20 mm; (3) with constant d, increasing a/h favors the reinforcement effect of UHPC on the beams; (4) as V_SF increases, the crack extension stage in the U+BNC beam becomes more gradual, with higher toughness and flexural properties; therefore, the best mechanical properties are achieved at a V_SF of 3%. Full article

Neuroblastoma is the most prevalent solid tumor in early childhood, with a 5-year overall survival rate of 40–60% in high-risk cases. Therefore, the identification of novel biomarkers for the diagnosis, prognosis, and therapy of neuroblastoma is crucial for improving the clinical outcomes of these patients. In this study, we conducted the whole-exome sequencing of 48 freshly frozen tumor samples obtained from the Biobank. Somatic variants were identified and selected using a bioinformatics analysis pipeline. The mutational signatures were determined using the Mutalisk online tool. Cancer driver genes and druggable mutations were predicted using the Cancer Genome Interpreter. The most common mutational signature was single base substitution 5. MUC4, MUC16, and FLG were identified as the most frequently mutated genes. Using the Cancer Genome Interpreter, we identified five recurrent cancer driver mutations spanning MUC16, MUC4, ALK, and CTNND1, with the latter being novel and containing a missense mutation, R439C. We also identified 11 putative actionable mutations including NF1 Q1798*, Q2616*, and S636X, ALK F1174L and R1275Q, SETD2 P10L and Q1829E, BRCA1 R612S, NOTCH1 D1670V, ATR S1372L, and FGFR1 N577K. Our findings provide a comprehensive overview of the novel information relevant to the underlying molecular pathogenesis and therapeutic targets of neuroblastoma. Full article

Placenta accreta spectrum (PAS) disorders are characterized by abnormal trophoblastic invasion into the myometrium, leading to significant maternal health risks. PAS includes placenta accreta (invasion < 50% of the myometrium), increta (invasion > 50%), and percreta (invasion through the entire myometrium). The condition is most associated with previous cesarean deliveries and increases in chance with the number of prior cesarians. The increasing global cesarean rates heighten the importance of early PAS diagnosis and management. This review explores genetic expression and key regulatory processes, such as apoptosis, cell proliferation, invasion, and inflammation, focusing on signaling pathways, genetic expression, biomarkers, and non-coding RNAs involved in trophoblastic invasion. It compiles the recent scientific literature (2014–2024) from the Scopus, PubMed, Google Scholar, and Web of Science databases. Identifying new biomarkers like AFP, sFlt-1, β-hCG, PlGF, and PAPP-A aids in early detection and management. Understanding genetic expression and non-coding RNAs is crucial for unraveling PAS complexities. In addition, aberrant signaling pathways like Notch, PI3K/Akt, STAT3, and TGF-β offer potential therapeutic targets to modulate trophoblastic invasion. This review underscores the need for interdisciplinary care, early diagnosis, and ongoing research into PAS biomarkers and molecular mechanisms to improve prognosis and quality of life for affected women. Full article

In this manuscript, a novel presenilin-2 (PSEN2) mutation, Val226Ala, was found in a 59-year-old Korean patient who exhibited rapid progressive memory dysfunction and hallucinations six months prior to her first visit to the hospital. Her Magnetic Resonance Imaging (MRI) showed brain atrophy, and both amyloid positron emission tomography (PET) and multimer detection system-oligomeric amyloid-beta (Aβ) results were positive. The patient was diagnosed with early onset Alzheimer’s disease. The whole-exome analysis revealed a new PSEN2 Val226Ala mutation with heterozygosity in the 5th transmembrane domain of the PSEN2 protein near the lumen region. Analyses of the structural prediction suggested structural changes in the helix, specifically a loss of a hydrogen bond between Val226 and Gln229, which may lead to elevated helix motion. Multiple PSEN2 mutations were reported in PSEN2 transmembrane-5 (TM5), such as Tyr231Cys, Ile235Phe, Ala237Val, Leu238Phe, Leu238Pro, and Met239Thr, highlighting the dynamic importance of the 5th transmembrane domain of PSEN2. Mutations in TM5 may alter the access tunnel of the Aβ substrate in the membrane to the gamma-secretase active site, indicating a possible influence on enzyme function that increases Aβ production. Interestingly, the current patient with the Val226Ala mutation presented with a combination of hallucinations and memory dysfunction. Although the causal mechanisms of hallucinations in AD remain unclear, it is possible that PSEN2 interacts with other disease risk factors, including Notch Receptor 3 (NOTCH3) or Glucosylceramidase Beta-1 (GBA) variants, enhancing the occurrence of hallucinations. In conclusion, the direct or indirect role of PSEN2 Val226Ala in AD onset cannot be ruled out. Full article

Variations in species distribution, population structure, and behavior can provide a portfolio effect that buffers populations against rapid environmental change. Although diversity has been identified as a goal for effective resource management and genetic and demographic tools have been developed, life history remains challenging to quantify. In this study, we demonstrate a novel metric of life history diversity using telemetry data from migratory fish. Here, we examined diversity in the outmigration behavior of juvenile Chinook salmon (Oncorhynchus tshawytscha) released in the Sacramento River, California, between 2007 and 2017. In this synthesis, we examined a wide variety of landscape and demographic drivers at high resolution by incorporating many individual telemetry studies, with variability in release location by year, environmental conditions, and all runs of salmon that are present in the watershed. When years were grouped by shared hydrologic conditions, variation in travel time was significantly higher in wet years. Further, our model showed a negative effect of warm temperatures at low flows on the variation in migration movements. This suggests that enhanced hydrologic connectivity increases the variation in migration time, a representation of habitat complexity and biocomplexity, despite the degraded state of this watershed and the weakened state of these populations. Variation in migration behavior could buffer species from current and future environmental changes, such as climate effects on precipitation and temperature. Hence, behavioral metrics generated from telemetry studies can be used to understand life history diversity and the potential effects of environmental fluctuations. Full article

Coronodon includes species of basal toothed mysticetes that were initially interpreted as engaging in raptorial feeding and dental filtration. Here, the feeding of this extinct genus is revisited based on recently described specimens and species. Associations between tooth position and types of dental wear were tested, and evidence for feeding behaviors was tabulated using scores from 14 craniodental characters, each mapped onto five alternate phylogenetic hypotheses. Individual character states were interpreted as being supportive, neutral, or contradictory evidence to raptorial feeding, suction feeding, baleen filtration, or dental filtration. Wear in Coronodon was found to be significantly more concentrated on mesial teeth, mesial cusps, higher cusps, and upper teeth. Upper teeth also had mesial cusps more worn than distal cusps, inconsistent with predictions of the dental filtration hypothesis. Wear in notches was correlated with wear on neighboring cusps, and side wear was concentrated on occlusal sides, suggesting both were caused by raptorial feeding. These observations raise the possibility that raptorial feeding was the primary, and maybe even the only, mode of feeding for Coronodon. The feeding scores of reconstructed ancestors leading to crown mysticetes typically display a stepwise decrease in raptorial feeding, a stepwise increase in baleen filtration, and, occasionally, an intermediate but weakly supported stage of dental filtration. For most toothed mysticetes, there is little evidence for or against suction feeding. The method we have developed for studying the origin of baleen can be expanded and allows for multiple hypotheses to be tested without undue emphasis on any particular taxon or set of characters. Full article

Cancer is well recognized as a leading cause of mortality. Although surgery tends to be the primary treatment option for many solid cancers, cancer surgery is still a risk factor for metastatic diseases and recurrence. For this reason, a variety of medications has been adopted for the postsurgical care of patients with cancer. However, conventional medicines have shown major challenges such as drug resistance, a high level of drug toxicity, and different drug responses, due to tumor heterogeneity. Nanotechnology-based therapeutic formulations could effectively overcome the challenges faced by conventional treatment methods. In particular, the combined use of nanomedicine with natural phytochemicals can enhance tumor targeting and increase the efficacy of anticancer agents with better solubility and bioavailability and reduced side effects. However, there is limited evidence in relation to the application of phytochemicals in cancer treatment, particularly focusing on nanotechnology. Therefore, in this review, first, we introduce the drug carriers used in advanced nanotechnology and their strengths and limitations. Second, we provide an update on well-studied nanotechnology-based anticancer therapies related to the carcinogenesis process, including signaling pathways related to transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), Wnt, poly(ADP-ribose) polymerase (PARP), Notch, and Hedgehog (HH). Third, we introduce approved nanomedicines currently available for anticancer therapy. Fourth, we discuss the potential roles of natural phytochemicals as anticancer drugs. Fifth, we also discuss the synergistic effect of nanocarriers and phytochemicals in anticancer therapy. Full article

In the complex clutter background, the clutter center frequency is not fixed, and the spectral width is wide, which leads to the performance degradation of the traditional adaptive clutter suppression method. Therefore, an adaptive clutter intelligent suppression method based on deep reinforcement learning (DRL) is proposed. Each range cell to be detected is regarded as an independent intelligence (agent) in the proposed method. The clutter environment is interactively learned using a deep learning (DL) process, and the filter parameter optimization is positively motivated by the reinforcement learning (RL) process to achieve the best clutter suppression effect. The suppression performance of the proposed method is tested on simulated and real data. The experimental results indicate that the filter notch designed by the proposed method is highly matched with the clutter compared with the existing adaptive clutter suppression methods. While suppressing the clutter, it has a higher amplitude-frequency response to signals at non-clutter frequencies, thus reducing the loss of the target signal and maximizing the output signal-to-clutter and noise rate (SCNR). Full article

Cancer cachexia (CC) continues to challenge clinicians by massively impairing patients’ prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac cachexia as characterized by atrophy, compromised metabolism, innervation and function of the myocardium through factors awaiting clarification for therapeutic targeting. Because monoamine oxidase-A (MAO-A) is a myocardial source of H₂O₂ and implicated in myofibrillar protein catabolism and heart failure, we presently studied myocardial MAO-A expression, inflammatory cells, and capillarization together with transcripts of pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic signals (by qRT-PCR) in a 3x-transgenic (LSL-Kras^G12D/+; LSL-TrP53^R172H/+; Pdx1-Cre) mouse model of orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) mice. Moreover, we evaluated the effect of MAO-A inhibition by application of harmine hydrochloride (HH, 8 weeks, i.p., no sham control) on PDAC-related myocardial alterations. Myocardial MAO-A protein content was significantly increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with an increased percentage of atrogin-1+ (p < 0.001), IL-1β+ (p < 0.01), COX2+ (p < 0.001), and CD68+ (p > 0.05) cells and enhanced transcripts of pro-inflammatory IL-1β (2.47-fold), COX2 (1.53-fold), TNF (1.87-fold), and SOCS3 (1.64-fold). Moreover, PDAC was associated with a reduction in capillary density (−17%, p < 0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3. Importantly, HH treatment largely reversed the PDAC-related increases in atrogin-1+, IL-1β+, and TNF+ cell fraction as well as in COX2, IL-1β, TNF, and SOCS3 transcripts, whereas capillary density and KDR transcripts failed to improve. In mice with PDAC, increased myocardial pro-atrophic/-inflammatory signals are attributable to increased expression of MAO-A, because they are significantly improved with MAO-A inhibition as a potential novel therapeutic option. The PDAC-related loss in myocardial capillary density may be due to other mechanisms awaiting evaluation with consideration of cardiomyocyte size, cardiac function and physical activity. Full article

Sling configurations significantly influence the coupled dynamics of the helicopter with slung load system (HSLS), resulting in alterations to handling qualities (HQs) that remain inadequately understood. This study introduces a computer-oriented, generalized method for constructing the HSLS model with various sling configurations. To evaluate the HQs of 1-point, 2-point, and 4-point sling configurations, both the stability and response criteria outlined in ADS-33E and a newly proposed criterion for slung loads towards the updated ADS-33F were employed. Modal analysis was conducted to elucidate the coupled mechanisms of the HSLS under different sling configurations. The findings reveal that the dynamics of the main rotor can attenuate the lateral swing motions of the load in the 4-point sling configuration. While multiple-point sling configurations can enhance the helicopter’s bandwidth, they also amplify the magnitude notch in the helicopter’s response. Nevertheless, when a larger hook distance is employed, the notch frequency is sufficiently distant from the load swing bandwidth, leading to a reduced degradation in HQs. A 4-point configuration with lateral and longitudinal hook distances equal to twice the width and length of the slung load is recommended in practice to achieve sufficient swing stability and mitigate HQ degradation. Full article

This work deals with the effects of two individual isothermal aging experiments (450 °C/5000 h and 700 °C/2500 h) and the subsequent room-temperature electrolytic hydrogen charging of TP316H stainless steel on its Charpy V-notch (CVN) impact toughness and fracture behavior at room temperature. Microstructural analyses revealed that aging at 700 °C resulted in the abundant precipitation of intermediary phases, namely, the Cr₂₃C_6-based carbide phase and Fe₂Mo-based Laves phase, whereas aging at 450 °C resulted in much less pronounced precipitation of mostly intergranular Cr₂₃C₆-based carbides. The matrix phase of 700 °C-aged material was completely formed of austenitic solid solution with a face-centered cubic (FCC) crystal structure, whereas an additional formation of ferritic phase with a base-centered cubic (BCC) structure was detected in 450 °C-aged material. The performed microstructure observations correlated well with the obtained values of CVN impact toughness, i.e., a sharp drop in the impact toughness was observed in the material aged at 700 °C, whereas negligible property changes were observed in the material aged at 450 °C. The initial, solution-annealed (precipitation-free) TP316H material exhibited a notable hydrogen toughening effect after hydrogen charging, which has been attributed to the hydrogen-enhanced twinning-induced plasticity (TWIP) deformation mechanism of the austenitic solid solution. In contrast, both aging expositions resulted in significantly lowered hydrogen embrittlement resistance, which was likely caused by hydrogen trapping effects at the precipitate/matrix interfaces in thermally aged materials, leading to a reduced TWIP effect in the austenitic phase. Full article

Epigenetic changes regulate gene expression through histone modifications, chromatin remodeling, and protein translation of these modifications. The PRC1 and PRC2 complexes shape gene repression via histone modifications. Specifically, the CBX protein family aids PRC1 recruitment to chromatin, impacting the progressive multistep process driving chromatin silencing. Among family members, CBX3 is a complex protein involved in aberrant epigenetic mechanisms that drive lung cancer progression. CBX3 promotes lung tumorigenesis by interacting with key pathways such as PI3K/AKT, Ras/KRAS, Wnt/β-catenin, MAPK, Notch, and p53, leading to increased proliferation, inhibition of apoptosis, and enhanced resistance to therapy. Given our current lack of knowledge, additional research is required to uncover the intricate mechanisms underlying CBX3 activity, as well as its involvement in molecular pathways and its potential biomarker evaluation. Specifically, the dissimilar roles of CBX3 could be reexamined to gain a greater insight into lung cancer pathogenesis. This review aims to provide a clear overview of the context-related molecular profile of CBX3, which could be useful for addressing clinical challenges and developing novel targeted therapies based on personalized medicine. Full article

Carbon fiber-reinforced plastic (CFRP) is a lightweight material. The automotive industry has focused on producing a steel/CFRP hybrid part to reduce overall weight. After manufacturing, delamination can occur at the interface between the CFRP and steel owing to the hybrid part constituting dissimilar materials. However, most studies have focused only on designing the manufacturing processes for the hybrid part or evaluating the adhesive used at the interface. Therefore, it is necessary to predict the behavior of the interface after demolding the hybrid part. This study aimed to predict the interface behavior of a steel/CFRP hybrid part by considering its forming and cohesive properties. First, double cantilever beam (DCB) and end-notched flexure (ENF) tests were performed to obtain cohesive parameters, such as energy release rate of modes I and II (G_I, G_II). The experimentally obtained properties were applied to the bonding area of the hybrid part. Subsequently, a forming simulation was performed to obtain the stress of the steel blank in the hybrid part. The stress distribution after forming was utilized as the initial condition for spring-back simulation. Finally, the interface behavior of the hybrid part was predicted by a spring-back simulation. The simulation was conducted using the residual stress of steel outer and the cohesive properties on the interface, without the application of any external forces. The cases of spring-back simulation were divided as delamination occurrence and attached state. The simulation results for prediction of delamination occurrence and bonding showed good agreement in both cases with experimental ones. The proposed method would contribute to expanding the manufacturing of the hybrid part by stamping and reducing the manufacturing cost by prediction of delamination occurrence. Full article